Prostate Cancer, the most prevalent male cancer and second leading cause of male cancer death, is currently detected by screening PSA and physical examination and confirmed with TRUS-guided prostate biopsy. Current diagnostic sensitivity is limited by poor visualization of tumor and inadequate sampling. Our fundamental hypothesis is that sonoelastography imaging can enable the detection of prostate cancer that otherwise appears normal in conventional in-vivo US imaging. A corollary of this hypothesis is that 3D sonoelastography can demarcate and help to calculate the volume of a suspected tumor region. Sonoelastic ultrasound imaging will enable earlier prostate cancer diagnosis due to better biopsy guidance and fewer false negative biopsies. Three-dimensional tumor volume analysis will provide quantification and localization for customized treatment, including tumor boost dose in brachytherapy. Our progress to date has led to new information regarding basic elements of sonoelastography including aliasing and modal patterns, tissue frequency dependence and variable beam patterns; and the techniques of 3D image pathology fusion. Our in-vivo work has similarly identified variables of gain, frequency, source beam patterns, and attenuation, which need to be controlled. Our next phase of research will focus on the following three aims: Aim 1: Develop the (currently unknown) theoretical and experimental characterization of the frequency dependent elastic properties of the normal prostate and of the prostate with benign and malignant conditions of high prevalence. (Year 1, with later extensions) Aim 2: Refine and advance our 3D Sonoelastography systems to increase the sensitivity, linearity, spatial resolution, and vibration frequency range so as to increase the detectability of cancer. (Year 1: 25 patients) Aim 3: Apply the results of aims 1 and 2 to evaluate the clinical utility of in-vivo prostate cancer detection by sonoelastography. (Years 2-4: 90 patients)